The prostate gland is a tiny walnut-shaped gland found in men’s pelvic. It’s right adjacent to the bladder and can be checked with a digital rectal exam. Prostate cancer is a type of cancer that starts in the prostate gland and spreads throughout the body. By breaking out from a prostate tumour, prostate cancer cells can spread and migrate to other parts of the body via blood arteries or lymph nodes.
Some of the current prostate cancer treatments are radiation therapy or combination therapy, non-steroidal antiandrogens, steroidal administration, chemotherapy, and surgery. Although these various treatment options can help to slow the progression of prostate cancer, they are also linked to other disorders that impact sexual and urinary function. As a result, prostate cancer research is focused on developing enhanced treatment options to avoid some of the difficulties that can arise. Androgen ablation therapy is a treatment for prostate cancer that inhibits the action of the androgen receptor (AR). The ability of prostate cancer to respond to testosterone stimulation is characterised as androgen-sensitive or androgen-insensitive.
Androgens stimulate prostate epithelial development and survival by binding to and activating the androgen receptor (AR). The AR–androgen complex works as a nuclear transcription factor for the activation of genes that promote the synthesis of prostate-specific antigen (PSA) and proteins involved in cell proliferation after intranuclear compartmentalization from the cytoplasm and DNA binding. Early-stage prostate cancer relies largely on AR activation for survival, although recurrence is typically marked by androgen-independent tumours due to adaptations to low androgen levels. Surrogate AR pathways arise when signalling is enhanced due to increased receptor sensitivity, or when androgen binding is not required at all. Prostate tumours that lack AR function skip androgen receptor signalling and activate other survival pathways, allowing them to spread.
Curcumin has been shown in multiple studies to induce apoptosis and inhibit prostate cancer proliferation in both in vitro and in vivo testing by interfering with several cellular pathways, including nuclear factor kappa B, epidermal growth factor, and mitogen-activated protein kinase. Curcumin compounds with increased solubility and anticancer effectiveness have been developed due to their low bioavailability, low cancer-killing potency, and numerous biological effects. Because curcumin has a low bioavailability, the amounts required to exert anticancer action in patients’ blood plasma are difficult to achieve. As a result, much effort has been expended in the synthesis of curcumin derivatives with effective anticancer activities and lower concentration values than curcumin.
When compared to curcumin, the anticancer activity of the curcumin derivative was increased, but the therapeutic efficacy and method of action are yet unknown, which is important to address because curcumin targets numerous signalling pathways. Dimethyl curcumin is another curcumin derivative that increases androgen receptor (AR) degradation and has been used to treat prostate cancer. According to the research on curcumin derivatives’ structure-activity relationships, the presence of a beta-diketone and a coplanar hydrogen donor group hybrid is significant for antiandrogenic activity in the treatment of prostate cancer.
Curcumin has been demonstrated to reduce the viability, proliferation, survival, migration/invasion, and adhesion of several human prostate cancer cells in vitro experiments. Curcumin inhibited both androgen-sensitive and androgen-insensitive prostate cancer cells by targeting a number of signalling pathways involved in cellular function regulation. Curcumin’s antiproliferative, antisurvival, and anti-migratory effects in prostate cancer cells could be due to signal transduction pathway inhibition, decreased nuclear factor kappa B activation and increased proapoptotic caspase and PARP(protein enzyme) cleavage, and inhibition of antiapoptotic Bcl-2 family proteins. Curcumin could also induce cell-cycle arrest and boost autophagy in prostate cancer cell lines.
On the other hand, curcumin has also been proven to decrease the growth/volume, formation, development, proliferation, and angiogenesis of prostate cancer tumours while increasing apoptosis in vivo tests. Both androgen-sensitive and androgen-insensitive prostate cancer cells were xenografted into mice, resulting in these outcomes. Curcumin may inhibit prostate tumour growth and progression by inhibiting protein kinase B expression and activation, decreasing nuclear factor kappa B activation, inhibiting the anti-apoptotic proteins Bcl-2 and Bcl-xL, increasing expression of the pro-apoptotic proteins Bax and Bak, and increasing PARP (protein enzyme) and caspase expression. The results of the in vivo experiments are consistent with those of the in vitro trials.
Curcumin is a promising option for the development of novel anticancer pharmacological drugs due to its low toxicity and downregulation of cell growth in combination with increased activity of programmed cell death both in vitro and in vivo. Future in vitro studies should concentrate on using cell culture parameters like varied oxygen levels and glucose concentrations to acquire data that better represents the tumour microenvironment seen in vivo. Furthermore, more research using normal prostate epithelium is needed to see if curcumin can distinguish between malignant and healthy tissue when interfering with signalling pathways.
Researchers will require several clinical prostate cancer cell lines to correctly establish curcumin dosage and to study if curcumin has powerful effects against prostate cancer in vivo. Finally, clinical trials are needed to determine whether curcumin is useful against human prostate cancer.