Curcumin-albumin conjugates as an effective anti-cancer agent with immunomodulatory properties
Authors: Lissy K Krishnan
S R Aravind
Journal: International Immunopharmacology (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Anticancer drug; Aqueous solubility; Bioavailability; Curcumin; Drug efficiency
Affiliations: Thrombosis Research Unit, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Trivandrum, Kerala, India., Thrombosis Research Unit, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Trivandrum, Kerala, India. Electronic address: .

Abstract:  Curcumin (diferuloylmethane) is an active ingredient in turmeric (Curcuma longa) with anti-inflammatory, antioxidant, chemopreventive, chemosensitization, and radiosensitization properties. Conjugation of curcumin (Curc) to albumin (Alb) has been found to increase the aqueous solubility of the drug. The current study aimed to prove the safe use of the Curc-Alb conjugate in animals and to demonstrate that it retains drug action both in vitro and in vivo. Dalton's lymphoma ascites (DLA) cell viability was inhibited by the Curc-Alb conjugate in a dose dependent manner in vitro, as evidenced by the MTT assay. Administration of up to 11.4 mg of conjugated curcumin per kg body weight to healthy animals was non-toxic both in terms of lethality and weight loss. Histological analysis of vital organs (kidney, liver and spleen) also did not show toxic effects. Favorable immuno-modulatory activity was observed after continuous administration of sub-acute doses of the conjugate which caused increase in total leukocyte count, platelet count, and viable cell count in bone marrow, and enhanced proliferation of lymphocyte in vitro upon culture. In vivo studies in the DLA tumor model in mice demonstrated that conjugated drug induces tumor reduction and prevention. Significant tumor reduction was observed when the Curc-Alb conjugate was administered intraperitoneally in DLA-induced mice after 1 day (prevention therapy) and 7 days (reduction therapy) of tumor induction. There was significant reduction in both tumor volume and tumor cell numbers in the treated animals as well as a marked increase in their mean survival time and percent increase in life span. The effect was greater when the conjugate was administered soon after inducing the tumor as compared to when treatment was started after allowing tumor to grow for 7 days. Thus, the results of the present study suggest that curcumin albumin conjugate has immunomodulatory and tumor growth inhibition properties. The study postulates the drug form has the potential to be used as an anticancer agent in affected human subjects. 

Retracted: No

PubPeer comments:
 The authors claim that they have an anti-cancer drug, which injected into peritoneal cavity within 24 h of tumor induction (injected cancer cells into) reduced tumor progression. First question: How did the authors prove that within 24 hr ascites tumor (Dalton s lymphoma ascites) was established? Then only it permits to evaluate the efficacy of injected drug. Injection of drug into peritoneal cavity within 24 hr after injecting cancer cells might have displaced the lymphoid cancer cells before the cells could attach to substratum and start proliferating. If lymphoid cells could be floating and surviving, and not eliminated from the peritoneal cavity, then these cells must be also affected by injected drug, even after 8 days of injection. Therefore, the Fig 6 , bottom images are not convincing. What is the explanation of the authors. The authors fail to convince with image data because images are not prepared and presented professionally. There is no scale bars in image, and the animals were not photographed keeping same zoom level and angle. The data raise suspicion about the claim that the anti-cancer drug is effective. The authors could present more reliable data to substantiate their claim. Authors reply solicited.. ,