Chloroquine diphosphate (Synonyms: DL-Chloroquine, NSC 14050)

Chloroquine diphosphate is used as an antimalarial drug and also functions to increase sensitivity of tumor cells to radiation and chemotherapy via inducing autophagy [1].

Chloroquine diphosphate has been reported as an adjuvant for radiation and chemotherapy for inducing cell autophagy to anti-cancer cells proliferation or metastasis [2]. The mechanism of chloroquine diphosphate inducing cells autophagy is arresting cells in G1, up-regulates the expression of p27 and p53 while down-regulates the expression of CDK2 and cyclin D1 [3].

Apart from anti-malarial, chloroquine diphosphate also has long been reported functioning in cell apoptosis. Pretreated CNE-2 human nasopharyngeal carcinoma cells with chloroquine diphosphate enhanced ionizing radiation induced cell apoptosis via increasing cells autophagic ratio [4]. When treated with mouse breast cancer 4T1 cells, chloroquine diphosphate treatment inhibited cellular proliferation and viability which resulted in cells apoptosis in a time- and dose- dependent manner [2]. In human colon cancer DLD-1 cells, combination of 5-FU and chloroquine diphosphate could inhibit cells proliferation via inducing autophagy [3].

In mouse model with 4T1 cells subcutaneous xenograft, chloroquine diphosphate treatment significantly inhibited tumor growth and tumor cells metastasis to the lung, thus enhanced the mice survival [2]. In BALB/c mice injected with colon26 cells subcutaneously, chloroquine diphosphate cooperated with 5-FU significantly enhanced the inhibition of tumor growth induced by 5-FU through increasing the ratio of apoptotic cells [5].

References:
[1].  Gewirtz, D.A., An autophagic switch in the response of tumor cells to radiation and chemotherapy. Biochem Pharmacol, 2014. 90(3): p. 208-11.
[2].  Jiang, P.D., et al., Antitumor and antimetastatic activities of chloroquine diphosphate in a murine model of breast cancer. Biomed Pharmacother, 2010. 64(9): p. 609-14.
[3].  Choi, J.H., et al., Chloroquine enhances the chemotherapeutic activity of 5-fluorouracil in a colon cancer cell line via cell cycle alteration. APMIS, 2012. 120(7): p. 597-604.
[4].  Zhou, Z.R., et al., Poly(ADP-ribose) polymerase-1 regulates the mechanism of irradiation-induced CNE-2 human nasopharyngeal carcinoma cell autophagy and inhibition of autophagy contributes to the radiation sensitization of CNE-2 cells. Oncol Rep, 2013. 29(6): p. 2498-506.
[5].  Sasaki, K., et al., Resistance of colon cancer to 5-fluorouracil may be overcome by combination with chloroquine, an in vivo study. Anticancer Drugs, 2012. 23(7): p. 675-82.