Journal Indonesian Journal of Cancer Chemoprevention

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Hilyatul Fadliyah, Nindya Budiana Putri, Ziana Walidah, Ika Putri Nurhayati, Muthi Ikawati, Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention, Volume 9, pp 68-77; doi:10.14499/indonesianjcanchemoprev9iss2pp68-77

Abstract:The development of cancer at an advanced stage is signed with metastasis that trigger the high of mortality caused breast cancer, possitive HER2 type mainly. Boesenbergia pandurata known as medicinal plant possessing anticancer potential due to the cytototoxic and antimetastatic characteristic of its active compound. The aim of this study is to observe the inhibitory of migration of Boesenbergia pandurata ethanolic extract (BPEE) in combination with doxorubicin (Dox) on MCF-7/HER2 cells. BPEE was prepared by 96% ethanol maceration. Under MTT assay, BPEE decreased the cells viability with IC50 value of 23 ± 3.9 μg/mL. Lamellipodia and wound healing assay analysis showed that BPEE (5 μg/mL) and its combination with doxorubicin (10 nM) inhibited cells migration after 48 hours observation, while gelatin zymography analysis showed that this combination did not affect the expression of MMP2 and MMP9 proteins, but single treatment of BPEE was more able to decrease the expression of both MMP. The combination with those concentrations inhibited the cells migration but not with the cells viability. Thus, BPEE is potential to be developed as antimetastatic agent. The mechanism itself needs to be explored further.
Nunuk Aries Nurulita, Anjar Mahardian Kusuma, Darsini Darsini, Weny Delvia, Veby Tri Yulianti
Indonesian Journal of Cancer Chemoprevention, Volume 9, pp 78-85; doi:10.14499/indonesianjcanchemoprev9iss2pp78-85

Abstract:Apple contains high concentration of phenolic compounds that protect cells from oxidative stress. The prolong exposure of free radicals may induce cell damage and premature cell aging. Both local and imported apple contain flavonoid, saponin, tannin, steroid, and terpenoid. The extract of local and imported apples showed low toxicity on NIH3T3 fibroblast cells, with IC50 value of 529 and 463 µg/mL, respectively. Both apple extracts (50 – 250 µg /mL) protected three-day-H2O2 induced-cell damage and cell death. Protective effect was observed as the viability increase of treated cells compared to untreated ones. The protective effect of both extracts were higher than the effect of vitamin C as standard antioxidant at this study. Both apple extracts could reverse cell damage caused by three-hour-high concentration H2O2 exposure, similar with vitamin C. Low concentration of both extracts (50 µg /mL) induced the increase of fibroblast cells’ proliferation kinetics. The extract of imported apple showed higher properties of protective, cell recovery and proliferation of fibroblast cells tha local apple, but not statistically significance. This study concludes that the extract of local and imported apples have high potency in cytoprotective effect and cell recovery of damaged cells caused by free radicals induction. Both apple extracts have high potency to be developed the candidate of antiaging and cells’ regeneration agent.Key words: antiaging, cell recovery, cytoprotective, NIH3T3 cells
Dhania Novitasari, Devyanto Hadi Triutomo, Fitriana Hayyu Arifah, Anselma Ivanawati, Zahrotul Ulum, Retno Murwanti
Indonesian Journal of Cancer Chemoprevention, Volume 9, pp 86-91; doi:10.14499/indonesianjcanchemoprev9iss2pp86-91

Abstract:Papaya bark is one of Indonesia's natural wealth that contains flavonoid compounds such as myricetin and kaempferol that included in the phytoestrogen compounds. The aim of this study is to examine the estrogenic effects of ethanolic extract of papaya peels (EEPP), on the development of mammae gland and the increasing of uterine weight. The in vivo test was performed with ovariectomy in Sprague Dawley female rats that caused the rats to be in an estrogen deficiency state. After 30 days of treatment, animals are sacrificed to take the uterus and mammae glands. Measurement of uterine weight and mammae gland are observed by hematoxylin-eosin staining method to know the lobulus development and AgNOR staining to determine the proliferation level of mammae gland epithelial cells. The test results showed that EEPP concentration of 500 and 1000 mg/kgBW were able to increase uterine weight and proliferation of mammae gland. From the results of this study, papaya bark has the potential to be one of the phytoestrogens compound to maintain female reproductive health and woman beauty.Keyword: ethanolic extract of papaya peels (EEPP), phytoestrogen, ovariectomized rats, uterine weight, mammae proliferation
Beni Lestari, Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention, Volume 9, pp 92-101; doi:10.14499/indonesianjcanchemoprev9iss2pp92-101

Abstract:The pumpkin, belongs to the family of Cucurbitaceae, is a well-known edible plant that has been frequently used as functional food or herbal medicine. Pumpkins contain rich unsaturated fatty acids, phytoestrogens and vitamins E in their seeds that have potential pharmaceutical, nutraceutical, and cosmeceutical properties. Information regarding their nutritional components and therapeutic properties of pumpkin seeds has expanded dynamically in the recent years and this review focus on the three main components of pumpkin seeds that described before. Several types of unsaturated fatty acids are the dominant composition in pumpkin seeds which can play a role in the disease prevention and promote health. Pumpkin seeds also contain the important phytoestrogen compounds, i.e., secoisolariciresinol and lariciresinol that have estrogenic-like effect such as preventing hyperlipidemia and osteoporosis for menopausal women. Phytoestrogens in pumpkin seeds also could be related to a reduced hormone-dependent tumor. Pumpkin seeds are rich in vitamin E contents as an emerging free radical scavenger, antiaging and antioxidant such as a-tocopherol and g-tocopherol. Findings of these studies prove that patents field for the innovation product of pumpkin seeds holds promise for the future along with their immense nutraceutical properties.
Ferry Sandra, Junita Briskila, Ketherin Ketherin
Indonesian Journal of Cancer Chemoprevention, Volume 9, pp 63-67; doi:10.14499/indonesianjcanchemoprev9iss2pp63-67

Abstract:Caffeic acid, a natural substance found majorly in fruits, grains, and herbs, is known to have therapeutic benefits. One of which is to inhibit bone resorption by targeting osteoclastogenesis through inhibition of the Cathepsin K, p38 Mitogen-activated Protein Kinase (MAPK), Nuclear Factor of Activated T-cells c1 (NFATc1) and Nuclear Factor kB (NFkB). Besides p38 MAPK, the c-Jun N-terminal kinase (JNK) / stress-activated protein kinases (SAPK), another member of MAPK family, has been reported to play important roles in osteoclastogenesis. Hence, current study was undertaken in order to investigate mechanism of Caffeic Acid towards JNK/SAPK pathway. Tartrate Resistant Acid Phosphatase (TRAP) staining was performed on caffeic acid-treated and RANKL-TNFα-induced RAW-D cells. Western blot analysis was performed to detect JNK/SAPK and phosphorylated-JNK/SAPK. Protein bands were quantified and statistically analyzed. Treatment of 10 μg/mL Caffeic Acid inhibited 20 ng/mL RANKL and 1 ng/mL TNFα-induced RAW-D differentiation into TRAP+ osteoclast-like polynuclear cells. Induction of 20 ng/mL of RANKL and 1 ng/mL of TNFα for 0.2 or 1 hour, significantly increase phosphorylation of JNK/SAPK as compared with control. Treatment of 10 µg/mL Caffeic Acid significantly inhibited the 20 ng/mL of RANKL and 1 ng/mL of TNFα-induced phosphorylation of JNK/SAPK. Taken together, Caffeic Acid could inhibit the RANKL and TNFα-induced osteoclastogenesis through JNK/SAPK.
Marsya Yonna, Hilyatul Fadliyah, Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention, Volume 9, pp 102-109; doi:10.14499/indonesianjcanchemoprev9iss2pp102-109

Abstract:Beside as a spice in Indonesian cooking, Fingerroot (Boesenbergia pandurata) regularly is used as a mixture of herbal medicine. Scientifically, the phytochemical content of the fingerroot rhizome showed some therapeutical effects such as antibacterial, anti-inflammatory, anti or pro-oxidant, and also anticancer. In this article, we summarize some studies especially about anticancer activity of fingerroot and its constituent coumpound. We found that fingerroot is capable of inhibiting various pathways of cell physiology processes. One potential pathway to be inhibited by fingerroot is Poly (ADP-ribose) polymerase (PARP) which has role in apoptotic induction. In the future, it is necessary to purify the extract to obtain maximum efficacy and also formulation studies of fingerroot will be interesting to do to.
Yonika Arum Larasati, Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention, Volume 9, pp 47-62; doi:10.14499/indonesianjcanchemoprev9iss1pp47-62

Abstract:Cinnamon (Cinnamomum spp.), an ancient spice, has been explored as a potential for medicinal purposes. Despite numerous studies about its potency in overcoming of numerous diseases, the potency as anti-cancer would be a challenge. This current article provides a review of the anti-cancer and chemoprevention potency of cinnamon and its major constituents: cinnamaldehyde, cinnamic acid, 2-hydroxycinnamaldehyde, 2-methoxycinnamaldehyde, and eugenol. Comprehensively, cinnamon and its constituents exhibit the anti-cancer and cancer prevention activities through various mechanisms: (1) anti-proliferation, (2) induction of cell death, (3) anti-angiogenesis, (4) anti-metastasis, (5) suppression of tumor-promoted inflammation, (6) immunomodulation, and (7) modulation of redox homeostasis; both in vitro and in vivo. Moreover, cinnamon also shows the synergistic anti-cancer effect with well-known anti-cancer drugs, such as doxorubicin, which support its potency to be used as a combination chemotherapeutic (co-chemotherapeutic) agent. However, further study should be established to determine the exact target molecule(s) of cinnamon in the cancer cells.Keywords: cinnamon, spice, cancer, anti-cancer, chemopreventive
Muthi Ikawati, Endah Puji Septisetyani
Indonesian Journal of Cancer Chemoprevention, Volume 9, pp 23-31; doi:10.14499/indonesianjcanchemoprev9iss1pp23-31

Abstract:The use of 5-fluorouracil (5-FU) in colon cancer as the primary chemotherapy has not been meet satisfactory effectiveness. Therefore, the development of new chemicals as a chemopreventive agent and a combination agent (co-chemotherapeutic agent) for colon cancer is important. Pentagamavunone-0 (2,5-bis-(4'-hydroxy-3'-methoxybenzylidine) cyclopentanone) (PGV-0), one of curcumin analogs, exhibits cytotoxic effect and apoptosis induction in various cancer cell lines, including colon cancer cell, better than curcumin. This study aimed to investigate the cytotoxic potency of PGV-0 in combination with 5-FU and their effects, in single or in combination, on cell cycle toward WiDr colon cancer cell line. The cells were treated with combination concentrations of PGV-0 and 5-FU, and examined by MTT cell viability assay. The value of combination index (CI) as a parameter of cytotoxic combination assay was measured by a combination index method. Cells were stained with propidium iodide and the cell cycle distribution was determined by flowcytometry. CI calculation showed additive effects between PGV-0 and 5-FU. Combination of PGV-0 and 5-FU gave synergism on cell cycle. Single treatment of PGV-0 increased apoptosis, illustrated as subG1-phase accumulation, stronger than single treatment of 5-FU. Meanwhile, combination of PGV-0 and 5-FU demonstrated S-phase arrest. Based on these results, it can be concluded that PGV-0 has the potential to be developed as a co-chemotherapeutic agent for colon cancer but still requires further tracking of its molecular mechanisms.Keywords: Pentagamavunone-0 (PGV-0), 5-fluorouracil (5-FU), colon cancer,combination, cell cycle
Laili Nailul Muna, Riris Istighfari Jenie
Indonesian Journal of Cancer Chemoprevention, Volume 9, pp 9-15; doi:10.14499/indonesianjcanchemoprev9iss1pp9-15

Abstract:One of the efforts to cure breast cancer is a combination of the chemotherapeutic agent with medicinal plants. This study was conducted to examine the activity of the combination between doxorubicin, curcuma rhizome (Curcuma xanthorriza Roxb.) ethanolic extract (CEE), and awar-awar leaves (Ficus septica Burm.f.) ethanolic extract (AAE) in inducing apoptosis and modulating the cell cycle progression in breast cancer T47D cells. The combination activity was performed using three series of concentration, 1/3; 1/6 and 1/12 of IC50, The combination index (CI) of doxorubicin, CEE and AEE was determined under MTT assay. The result showed that the combination of 10 µM, 5 µg/ml, 1 µg/ml concentrations of doxorubicin, CEE and AEE respectively result in synergistic effect with CI values less than 1. The treatment exhibited the cell accumulation in S phase (27.7%) against T47D breast cancer cells confirmed through cell cycle examination by flow cytometry. These results provided the evidence that CEE and the AEE can be developed as co-chemotherapeutic agents combined with doxorubicin to improve the effectiveness of breast cancer treatment.Keywords : Curcuma xanthorriza Roxb., Ficus septica Burm.f., doxorubicin, cell cycle.
Ika Nurzijah, Dina Ratna Juwita
Indonesian Journal of Cancer Chemoprevention, Volume 9, pp 41-46; doi:10.14499/indonesianjcanchemoprev9iss1pp41-46

Abstract:Clonorchiasis is a parasitic infection caused by food borne trematode, Clonorchis sinensis that is mainly prevalent in Asian countries, including South Korea, China, northern Vietnam, Japan, as well as far-eastern Russia, in which over 35 million people are the casualties. Clonorchiasis is characterized by the development of hepatic fibrosis. Upon chronic liver injury following the C. sinensis infection, hepatic fibrosis develops into cholangiocarcinoma with a concomitant genetic and epigenetic mutations. Cholangiocarcinoma represents important clinical manifestation of C. sinensis infection and causes high rate of morbidity. TGF- β/Smad signalling is known to initiate hepatic fibrosis following the hepatic injury. However, little is known about the role of TGF- β/Smad signalling during C. sinensis induced hepatic injury and the underlying contribution of TGF- β/Smad signalling in the development of cholangicarcinoma. The expression dynamic of TGF-β/Smad signalling and their role in the development of hepatic fibrosis in C. sinensis infected BALB/c mice have been investigated. Concomitantly but irrespective to C. sinensis infection, the role of hepatic epithelial TGF-β during hepatic fibrosis and the development of cholangiocarcinoma arising from hepatic epithelial cells have also been dissected. Both findings will be reviewed in this paper. Thereby, the link between TGF-β/Smad signalling, hepatic fibrosis during C sinensis infection, and cholangiocarcinoma could be drawn clearly.Keywords: Clonorchis sinensis, TGF-β/Smad signalling, Hepatic fibrosis, Cholangiocarcinoma
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