Authors: Akwasi Afrane Bediako & Raymond Ohene Gyan
Affiliation: Faculty of Biosciences, University For Development Studies, Ghana
Date: 01/11/2024
Cancer is one of the top 5 causes of mortality worldwide, making it a significant global issue. In Africa, the incidence of cancer is predicted to reach 1.28 million cases a year and 970,000 deaths annually by 2030 if unchecked [1].
Curcumin, derived from the Curcuma longa plant, is a useful therapeutic tool in the field of clinical cancer. Certain aggressive and recurring malignancies can be treated using curcumin’s antitumoral and chemopreventive properties.
Certain proteins, including transcription factors, inflammatory cytokines and enzymes, and gene products associated with cell survival and proliferation, can have their expressions and functions altered by curcumin.
Furthermore, curcumin lessens mitomycin’s harmful effects and it has demonstrated strong cytotoxicity against some cancer cell lines [2].
The specific administration of nanotechnology-derived curcumin formulations to malignancies might enhance their chemopreventive and chemotherapeutic properties. This brief review aims to explain the role curcumin plays in the antitumor processes in breast cancer cells [3].
Aerobic Glycolysis in Cancer Cells As An Energy Source.
A necessary condition for carcinogenesis is the dysregulation of cell proliferation. A population of tumor cells formed from clones proliferates as a result of abnormal proliferation caused by a single genetically modified cell. But to make this feasible, energy and biomass production are essential for enabling and maintaining unchecked cell growth.
Because there are fewer nutrients available in a tumor, cancer cells compete with other cell types in their microenvironments for those nutrients. As a result, unchecked cell division and tumor development alter metabolic demands and cellular availability of nutrients and oxygen, which encourages change in metabolism [2].
Nutrient availability in the tumor environment makes it critical for these cells to have a mechanism in place to meet their energy needs for growth and proliferation. Similarly, it has been shown that cancer cells exhibit the “Warburg Effect,” a modification in glucose metabolism.
Basically, instead of the more vigorous and effective oxidative phosphorylation that takes place in normal cells, cancer cells prefer metabolism via aerobic glycolysis, which leads to the buildup of lactate. Resistance to treatment and the advancement of cancer are both benefited by this change in cell metabolism. Compared to oxidative phosphorylation, which produces 36 ATPs per molecule of glucose, aerobic glycolysis only produces 2 ATPs, making it an inefficient method of producing ATP [4].
Nevertheless, since biomass creation takes precedence over energy generation, aerobic glycolysis continues to be the favored metabolic pathway for cancer cells. Thus, significant concentrations of carbon-rich metabolic intermediates produced by glycolysis in cancer cells may be used as starting points for the production of lipids, amino acids, or nucleotides. Particularly, glycolytic intermediates such as glucose-6-phosphate and fructose-6-phosphate, glyceraldehyde-3-phosphate, and 3-phosphoglycerate serve as substrates for the production of lipids, amino acids, and nucleotides [3].
Antioxidant and Anti-proliferative Effect of Curcumin
The antioxidant properties of curcumin are critical in their role as cancer-preventive agents. Reactive oxygen species (ROS), which are produced as byproducts of cellular metabolism, can promote oxidative stress when present in abundance. Oxidative stress plays a major role in damaging cellular components, including lipids, proteins, and DNA, which can therefore promote mutations and trigger carcinogenesis. Curcumin helps neutralize ROS, thereby reducing oxidative stress and protecting cells from potential damage that can lead to cancer. Breast cancer cells often exhibit increased oxidative stress compared to normal cells, which promotes cell proliferation and survival [5].
Curcumin Impact On The Oncogene Proteins Involved In Apoptosis And Proliferation
Natural curcumin has been demonstrated to cause apoptosis and limit the growth of several tumor cell types, making it a substance with great therapeutic promise. Research has indicated that it can inhibit tumors caused by carcinogens in mouse models. Curcumin substantially inhibited the development of human malignancies in both xenotransplant and orthotransplant animal models. When curcumin was administered alone, this anticancer activity was seen, and when it was coupled with radiation or chemotherapy, its efficacy was increased, indicating its potential as a supplemental treatment [6].
Curcumin had a significant effect in cellular models by causing apoptosis and G2/M phase cell cycle arrest in the MCF-7 breast cancer cells. It accomplished this by interfering with the kinetics of microtubule assembly, which is essential for cell division. Curcumin is a potent drug that can disrupt the development of cancer cells because it further amplifies its capacity to suppress cell proliferation by activating the mitotic checkpoint. Research on curcumin’s varied involvement in cancer inhibition and its hopeful future in oncological therapies is steadily expanding [3].
A research investigation by Zhou in 2020 on the effects of curcumin on breast cancer cells, especially MDA-MB-231 and MDA-MB-468, indicated that curcumin greatly boosted the apoptotic rates in these cells. The increase of cysteinyl aspartate-specific proteinase 9 (Caspase-9), a crucial enzyme implicated in the start of apoptosis, facilitated this pro-apoptotic action. Simultaneously, curcumin decreased the production of B-cell lymphoma-2 (Bcl-2), a protein that is essential for both boosting the survival of cancer cells and inhibiting their demise. Curcumin demonstrated its powerful capacity to induce programmed cell death and decrease the survival of aggressive breast cancer cells by efficiently tipping the balance towards apoptosis by increasing the levels of Caspase-9 and lowering Bcl-2 [6].
Table 1: Curcumin modes of action in cancer cells.
| Type of Study | Model | Dosage | Period | Effect | Ref |
| In vitro | MDA-MB-231 and MDA-MB-468 breast cancer cell | 10, 15, 20, 25, 30 and 35 µM | 24, 48 and 72 h | Inhibiting proliferation, invasion, and migration | [7] |
| In vitro | MCF-7 and MDA-MB-231breast cancer cells | 6.25, 25 and 100 µM | 24 h | Cytotoxicity effect | [8] |
| In vitro | MCF-7 and MDA-MB-231 breast cancer cells | 10, 15, 20, 25, 30, 35 and 40 µM | 24 and 48 h | Inhibiting cell viability, invasion, and migration. | [9] |
| In vitro | PC-3 and DU145 prostate cancer cells | 10, 20, 30, 40 and 50 µM | 12, 24 and 48 h | Promoting cell apoptosis | [10] |
CONCLUSION
Research on curcumin and cancer treatment offers a viable avenue for novel therapeutics. Their potential to produce more effective therapies is highlighted by their capacity to target various cancer-related pathways, including causing apoptosis, altering cancer cell metabolism, and decreasing oxidative stress.
Polyphenols such as curcumin have already shown notable effects on preclinical models. Further studies may open the door to incorporating these organic substances into conventional cancer treatments. As we learn more about their processes, curcumin may provide new avenues for improving patient outcomes and addressing the rising burden of cancer worldwide.
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