Aim Triple negative breast cancer cells (TNBC) are the population of breast cancer cells that are responsible for cancer recurrence and apoptosis resistance. Unfortunately, current therapies have limited efficacy to TNBC population due to apoptosis resistance and chemoresistance. Tumour suppressor p53 and survivin are primary targets for TNBC therapy. Consequently, a search for a natural compound which targets p53 and survivin is needed to further advance TNBC treatment. Curcuma longa extract (CL), a natural compound induces apoptosis in several cancer cells by targeting various molecules and possess fewer side effects. However, a possible potential of CL as p53- and survivin modulating agent in TNBC cells has not been investigated. Methods MDAMB-231 cells were treated with several concentration of CL, after which, viability, p53 gene expression, surviving protein expression, and caspase-3 protein expression were evaluated. Results After 24-h treatment, CL possessed cytotoxic effect with IC50 value of 13 μg/mL. Treatment with 1.625, 3.25, 6.5, and 13 μg/mL of CL resulted in 2.70-25.80% increase in caspase-3 expression levels followed by 94.60 – 21.60% decrease in survivin protein levels. CL induced remarkably p53 gene expression ratio up to 5-fold at 13 μg/mL. Survivin protein levels were inversely proportional to p53 accumulation levels. Low survivin protein levels combined with high levels of p53 accumulation were correlated to higher apoptotic rates. Conclusion p53 and survivin as molecular targets of CL contribute to caspase-3-dependent apoptosis in TNBC cells and this compound represents an attractive p53- and survivin modulating agent in TNBC.
Bray F, Ferlay J, Soerjomataram I. Global Cancer Statistics 2018 : GLOBOCAN Estimates of Incidence and mortality worldwide for 36 cancers in 185 countries. 2018. p. 394–424.
2.
Telli M, Carlson R. First-line chemotherapy for metastatic breast cancer. Clin Breast Cancer. 2009. p. 66–72.
3.
Nedeljkovi M, Damjanović A. Mechanisms of chemotherapy resistance in triple-negative breast cancerhow we can rise to the challenge. Cells. 2019. p. 957.
4.
Vyas D, Laput G, Vyas A. Chemotherapy-enhanced inflammation may lead to the failure of therapy and metastasis. Onco Targets Ther. 2014. p. 1015–23.
5.
Crabtree J, Miele L. Breast cancer stem cells. Biomedicines. 2018. p. 133–51.
6.
Lü X, Deng Q, Li H, Suo Z. Altered characteristics of cancer stem/initiating cells in a breast cancer cell line treated with persistent 5-FU chemotherapy. Exp Ther Med. 2011. p. 821–6.
7.
Amaral D, J, Xavier M, J, Steer J, C, et al. Targeting the p53 pathway of apoptosis. Curr Pharm Des. 2010. p. 2493–503.
8.
Li D, Hu C, Li H. Survivin as a novel target protein for reducing the proliferation of cancer cells (review). Biomed Reports. 2018. p. 399–406.
9.
Devarajan E, Sahin A, Chen J, Krishnamurthy R, Aggarwal N, Brun A, et al. Down-regulation of caspase 3 in breast cancer: a possible mechanism for chemoresistance. Oncogene. 2002. p. 8843–51.
10.
Choi J, Kim J, Lee H, Pak J, Shim B, Kim S. Reactive oxygen species and p53 mediated activation of p38 and caspases is critically involved in kaempferol induced apoptosis in colorectal cancer cells. J Agric Food Chem. 2018. p. 9960–7.
11.
Liu X, Jiang S, Tian X, Jiang Y. Expression of cleaved caspase-3 predicts good chemotherapy response but poor survival for patients with advanced primary triple-negative breast cancer. Int J Clin Exp Pathol. 2018. p. 4363–73.
12.
Kontomanolis E, Kalagasidou S, Pouliliou S, Anthoulaki X, Georgiou N, Papamanolis V. The Notch Pathway in Breast Cancer Progression. Sci World J. 2018. p. 1–12.
13.
Duo J, Ying G, Wang G, Zhang L. Quercetin inhibits human breast cancer cell proliferation and induces apoptosis via Bcl-2 and Bax regulation. Mol Med Rep. 2012. p. 1453–6.
14.
Ahmad R, Srivastava A, Khan M. Evaluation of in vitro anticancer activity of rhizome of {Curcuma} longa against human breast cancer and {Vero} cell lines. Int J Bot Stud. 2016. p. 1–6.
15.
Perrone D, Ardito F, Giannatempo G, Dioguardi M, Troiano G, Russo L, et al. Muzio L. Biological and therapeutic activities, and anticancer properties of curcumin (Review). Exp Ther Med. 2015. p. 1615–23.
16.
Lee D, Lee M, Kim J. Curcumin induces cell cycle arrest and apoptosis in human osteosarcoma (HOS) cells. Anticancer Res. 2009. p. 5039–44.
17.
Amalina N, Suzey M, Cahyono B. Cytotoxic activity of Hyptis pectinata extracts on MCF-7 human breast cancer cells. Indones J Cancer Chemoprevention. 2020. p. 1–6.
18.
Lee Y, Kim N, Suh Y, Lee C. Involvement of ROS in curcumin-induced autophagic cell death. Korean. J Physiol Pharmacol. 2011. p. 1–7.
19.
Balasubramanyam M, Koteswari A, Kumar R, Monickaraj S, Maheswari J, Mohan V. Curcumininduced inhibition of cellular reactive oxygen species generation: Novel therapeutic implications. J Biosci. 2003. p. 715–21.
20.
Amalina N, Nurhayati I, Meiyanto E. Doxorubicin induces lamellipodia formation and cell migration. Indones J Cancer Chemoprevention. 2017. p. 61.
21.
Cahyono B, Amalina N, Suzery M, Bima D. Exploring the Capability of Indonesia natural medicine secondary metabolite as potential inhibitors of SARS-CoV-2 proteins to prevent virulence of CO-VID-19: in silico and bioinformatic approach. 2021. p. 336–42.
22.
Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983. p. 55–63.
23.
Amalina N, Wahyuni S, Harjito. Cytotoxic effects of the synthesized Citrus aurantium peels extract nanoparticles against MDA-MB-231 breast cancer cells. J Phys Conf Ser. 2021. p. 32006.
24.
Mursiti S, Amalina N, Marianti A. Inhibition of breast cancer cell development using Citrus maxima extract through increasing levels of reactive oxygen species (ROS). J Phys Conf Ser. 1918.
25.
Suzery M, Cahyono B, Amalina N. Antiproliferative and apoptosis effect of hyptolide from Hyptis pectinata (L .) Poit on human breast cancer cells. 2020. p. 1–6.
26.
Ikawati M, Jenie R, Utomo R, Amalina N, Ilmawati N, Kawaichi G, et al. Genistein enhances cytotoxic and antimigratory activities of doxorubicin on 4T1 breast cancer cells through cell cycle arrest and ROS generation. J Appl Pharm Sci. 2020. p. 95–104.
27.
Suzery M, Cahyono B, Amalina N. Citrus sinensis (L) peels extract inhibits metastasis of breast cancer cells by targeting the downregulation matrix metalloproteinases-9. Open Access Maced J Med Sci. 2021. p. 464–9.
28.
Jenie R, Amalina N, Ilmawati G, Utomo R, Ikawati M, Khumaira A, et al. Cell cycle modulation of CHO-K1 cells under genistein treatment correlates with cells senescence, apoptosis and ROS level but in a dose-dependent manner. Adv Pharm Bull. 2019. p. 453–61.
29.
Yerlikaya A, Okur E, Ulukaya E. The p53-independent induction of apoptosis in breast cancer cells in response to proteasome inhibitor bortezomib. Tumor Biol. 2012. p. 1385–92.
30.
Suzery M, Cahyono B. Amalina ND Antiproliferative and apoptosis effect of hyptolide from Hyptis pectinata (L.) Poit on human breast cancer cells. J Appl Pharm Sci. 2020. p. 1–6.
31.
Fu H, Wang C, Yang D, Wei Z, Xu J, Hu Z, et al. Curcumin regulates proliferation, autophagy, and apoptosis in gastric cancer cells by affecting PI3K and P53 signaling. J Cell Physiol. 2018. p. 4634–42.
32.
Talib W, Sa AH, Ali M, Al-Yasari I, Ali M. Role of curcumin in regulating p53 in breast cancer: An overview of the mechanism of action. Breast Cancer Targets Ther. 2018. p. 207–17.
33.
Larasati Y, Yoneda-Kato N, Nakamae I, Yokoyama T, Meiyanto E, Kato J. Curcumin targets multiple enzymes involved in the ROS metabolic pathway to suppress tumor cell growth. Sci Rep. 2018. p. 1–13.
34.
Jaiswal P, Goel A, Mittal R. Survivin: A molecular biomarker in cancer. Indian J Med Res. 2015. p. 389–97.
35.
Guo L, Da, Chen X, Hu Y, Yu Z, Wang D, et al. Curcumin inhibits proliferation and induces apoptosis of human colorectal cancer cells by activating the mitochondria apoptotic pathway. Phyther Res. 2013. p. 422–30.
36.
Safa A. Resistance to cell death and its modulation in cancer stem cells. Physiol Behav. 2017. p. 139–48.
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