Efficiency of All-Trans Retinoic Acid on Gastric Cancer: A Narrative Literature Review

Abstract

Gastric cancer (GC) is the third leading cause of cancer-related death worldwide with a five-year survival rate of around 25%, and 4% when diagnosed at a metastatic stage. Cancer stem cells (CSC) have recently been characterized as being responsible for resistance to radio/chemotherapies and metastasis formation, opening up perspectives for new targeted therapies. Those CSCs express biomarkers such as cluster of differentiation 44 (CD44) and display high aldehyde dehydrogenase activity that converts vitamin A-derived retinal into retinoic acids. All-trans retinoic acid (ATRA), which has pro-differentiating properties, has revolutionized the prognosis of acute promyelotic leukemia by increasing its remission rate from 15% to 85%. Recent studies have started to show that ATRA also has an anti-tumoral role on solid cancers such as GC. The purpose of this review is therefore to summarize the work that evaluated the effects of ATRA in GC and to evaluate whether its anti-cancerous action involves gastric CSCs targeting. It has been demonstrated that ATRA can block the cell cycle, enhance apoptosis, and decrease gastric CSCs properties in GC cell lines, tumorspheres, and patient-derived xenograft mice models. Therefore, retinoids and new synthetic retinoids seem to be a promising step forward in targeted therapy of gastric CSC in combination with existing chemotherapies. Future studies should probably focus on these points.

Reduction of Serum Concentrations and Synergy between Retinol, β-Carotene, and Zinc According to Cancer Staging and Different Treatment Modalities Prior to Radiation Therapy in Women with Breast Cancer

“…Recently, the literature has been pointing out a relationship between nutrients with antioxidant function and cancer therapy. Among the antioxidants studied, some have been highlighted, such as vitamin A due to its role in cancer therapy, given its chemoprotective and antioxidant role, which is able to decrease, in the short and long term, the harmful effects of cancer treatment [8][9][10].…”

Stathmin gene silencing suppresses proliferation, migration and invasion of gastric cancer cells via AKT/sCLU and STAT3 signaling

“…GC is the third most common cause of cancer-related mortality worldwide, and has attracted much attention due to its relatively high rates of incidence and mortality (3). Although surgical resection and chemotherapy are the mainstream methods of treating this malignancy, patients suffering from advanced stage GC have poor prognoses and high mortality rates.…”

“…Globally, gastric cancer (GC) is the fifth most common malignant tumor and the third leading cause of cancer-related mortality (1). The 5-year survival rate of GC remains low (25%) (2,3). Although great progress has been made in the availability of treatment techniques for GC, the prognosis for GC patients remains poor due to the biological properties of tumor cells, including a high propensity for invasiveness and metastasis, rapid proliferation, and anti-apoptotic behavior (4).…”

Combinations of vitamins A, D2 and D3 have synergistic effects in gastric and colon cancer cells

“…was first reported in 1926, when it was observed that that gastric cancers were increased in rats fed a vitamin A-deficient diet [12][13]. Later experimental data demonstrated that all-trans retinoic acid (ATRA) was effective against leukemia and induced the differentiation of HL-60 leukemia cells, as well as inhibited the growth of gastric and breast cancers [14][15]. ATRA is the preferred isomer as compared with the cis-retinoic acid isomer, and it has been demonstrated that ATRA has better efficiency both in vitro and in vivo [14][15].…”

“…Later experimental data demonstrated that all-trans retinoic acid (ATRA) was effective against leukemia and induced the differentiation of HL-60 leukemia cells, as well as inhibited the growth of gastric and breast cancers [14][15]. ATRA is the preferred isomer as compared with the cis-retinoic acid isomer, and it has been demonstrated that ATRA has better efficiency both in vitro and in vivo [14][15]. Thus, along with vitamin D, vitamin A (retinol, retinoic acid) and the carotenoids have also been shown to have a significant impact on cancer chemoprevention and treatment, most notably in cancers derived from epithelial tissues [12][13][14][15][16].…”