Volume 5, Issue 1, January 2015, Pages 35–41
Open Access
Original article
Anticancer activity of Aristolochia ringens Vahl. (Aristolochiaceae)
- Open Access funded by Center for Food and Biomolecules, National Taiwan University
- Under a Creative Commons license
Abstract
Cancer
is a leading cause of death worldwide and sustained focus is on the
discovery and development of newer and better tolerated anticancer drugs
especially from plants. The sulforhodamine B (SRB) in vitro cytotoxicity assay, sarcoma-180 (S-180) ascites and solid tumor, and L1210 lymphoid leukemia in vivo models were used to investigate the anticancer activity of root extracts of Aristolochia ringens Vahl. (Aristolochiaceae; 馬兜鈴 mǎ dōu líng). AR-A001 (IC50
values of 20 μg/mL, 22 μg/mL, 3 μg/mL, and 24 μg/mL for A549, HCT-116,
PC3, and THP-1 cell lines, respectively), and AR-A004 (IC50
values of 26 μg/mL, 19.5 μg/mL, 12 μg/mL, 28 μg/mL, 30 μg/mL, and
22 μg/mL for A549, HCT-116, PC3, A431, HeLa, and THP-1, respectively),
were observed to be significantly active in vitro. Potency was highest with AR-A001 and AR-A004 for PC3 with IC50 values of 3 μg/mL and 12 μg/mL, respectively. AR-A001 and AR-A004 produced significant (p < 0.05–0.001)
dose-dependent inhibition of tumor growth in the S-180 ascites model
with peak effects produced at the highest dose of 120 mg/kg. Inhibition
values were 79.51% and 89.98% for AR-A001 and AR-A004, respectively. In
the S-180 solid tumor model, the inhibition of tumor growth was 29.45%
and 50.50% for AR-A001 (120 mg/kg) and AR-A004 (110 mg/kg),
respectively, compared to 50.18% for 5-fluorouracil (5-FU; 20 mg/kg).
AR-A001 and AR-A004 were also significantly active in the leukemia model
with 211.11% and 155.56% increase in mean survival time (MST) compared
to a value of 211.11% for 5-FU. In conclusion, the ethanolic (AR-A001)
and dichloromethane:methanol (AR-A004) root extracts of AR possess
significant anticancer activities in vitro and in vivo.
Graphical abstract
Keywords
- Anticancer activity;
- Aristolochia ringens;
- Cytotoxicity;
- Lymphoid leukemia;
- Solid tumor
1. Introduction
Cancer
is a deadly disease and about one in four people will get it in some
form during their lifetime; at the present time, about one in five of
all deaths are due to cancer.1
Normal diploid human cells multiply for a finite number of generations
and then enter a state of replicative senescence, but cancer cells can
proliferate indefinitely.2
About 12.7 million cancer cases and 7.6 million cancer deaths are
estimated to have occurred in 2008; of these, 56% of the cases and 64%
of the deaths occurred in the economically developing world.3
Surgery is useful in removing visible tumors, but may leave smaller
nests of cancer cells in the patient which continue to proliferate,
while radiation therapy is relatively imprecise as it can kill both
cancer cells and normal cells, and thus has toxic side effects which may
themselves be lethal to the patients.2
Chemotherapy with antiproliferative agents, including alkylating
agents, antimetabolites, antibiotics, and hormones, apart from being
complementary to surgical intervention and radiotherapy, is essential in
cases of metastasis.
According to Sikora et al,4
although 92 approved anticancer drugs are available for the treatment
of > 200 different tumor entities, effective therapies for most of
these tumors are lacking. Furthermore, out of the 92 registered drugs,
17 are considered by oncologists to be more broadly applicable and 12
additional agents are perceived as having certain advantages in some
clinical settings.5
Limitations in the application of chemotherapeutic agents include
toxicity, manifestation of deleterious side-effects, and a narrow margin
of error. These days, renewed and concerted efforts are geared towards
the discovery and development of newer and better tolerated anticancer
drugs, especially from natural products, mainly plants. New targets for
anticancer agent development are rapidly emerging in the post-genome
era, and improvements in protein structure determination, combinatorial
chemistry, and high-throughput small-molecule screens may accelerate the
generation of new agents to be studied in the clinic.6
Aristolochia ringens
Vahl. (Aristolochiaceae (AR); 馬兜鈴 mǎ dōu líng) is a glabrous bushy
climber native of tropical America, introduced to most West African
countries as a garden ornamental, and has become naturalized in roadside
bush in Sierra Leone, Ghana, Nigeria, 7 and DR Congo. 8
The plant is commonly called “Dutchman's pipe” and “Snake work” but
local names in Nigeria include “Ako-igun” (Yoruba, Southwest Nigeria)
and “Dumandutsee” (Hausa, Northern Nigeria). Preparations of the leaves,
roots, and whole plant have been reported to be used traditionally in
Nigeria for the treatment of diverse ailments including guinea worm,
skin diseases, typhoid, sores, as an antidote to snake poison, an
emmenagogue, and an anthelmintic remedy. 9 In South America, the plant is used for the treatment of snakebites, fever, ulcers, and colic, 10 while the root of the plant is used in Senegal as an antidote for snakebites. 11 Sonibare and Gbile 12 stated that the root of the plant is used in Southwest Nigeria for the treatment of asthma, while Soladoye et al 13
reported its use for the treatment of hemorrhoids. The
decoction/infusion of the root of the plant is also used as an
antidiabetic. 14 Antiinflammatory 15 and antitrypanosomal 16 activities of the plant have also been reported.
